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Simple Summary: Intraoperative radiation therapy (IORT) can be a useful treatment modality in patients with recurrent cervical or endometrial cancer. The existing literature on IORT use in recurrent gynecologic malignancies is limited by small sample sizes because few centers use IORT and few patients are ideal candidates. The aim of our study is to describe a modern cohort of patients who were considered for IORT and predict risk factors of morbidity and mortality. We found that appreciable survival gain can be achieved with the use of IORT, with factors such as ECOG performance status (ECOG PS), neoadjuvant chemotherapy/immunotherapy, pelvic sidewall involvement, whether exenteration was performed, and resection margin status influencing the risk of morbidity and/or mortality. Background/Objectives: Our objective was to describe the use of intraoperative radiation therapy (IORT) for the treatment of recurrent/persistent cervical or endometrial cancer and assess predictors of postoperative complications and 3-year mortality. Methods: In this multi-site retrospective study, data were abstracted for recurrent/persistent endometrial or cervical cancer patients who underwent IORT from June 2004 to May 2021. Complications were graded on the six-point Accordion scale. Variables associated with complications were analyzed with univariate logistic regression, while variables associated with death within 3 years were analyzed with Cox proportional hazards modeling. Survival was analyzed with the Kaplan–Meier method. Results: Eighty patients had planned IORT for recurrent/persistent endometrial (n = 35) or cervical cancer (n = 45). The mean age of the cohort was 56.8 years (SD = 13.7), and the median disease-free interval from primary disease to recurrence was 20.0 months (IQR 10.0–63.1). The overall survival at 3 years was 48.6% (95% CI: 38.3–61.6%) with a median survival of 2.8 years. Within 30 days postoperative, 16 patients (20.1%) had grade 3–5 complications and one death (1.3%) occurred. Factors associated with grade 3+ complication included ECOG PS 2–3 (OR 18.00, p = 0.04), neoadjuvant chemotherapy and/or immunotherapy (OR 6.98, p < 0.01), and pelvic sidewall involvement (OR 8.80, p = 0.04). Factors associated with death within 3 years of surgery included ECOG PS 2–3 (HR 8.97, p < 0.01), neoadjuvant chemotherapy and/or immunotherapy (HR 2.34, p = 0.03), whether exenteration was performed (HR 2.64, p = 0.01), and positive resection margin (HR 3.37, p < 0.01). Conclusions: In well-selected patients, IORT is a feasible and safe option for the treatment of recurrent/persistent gynecologic malignancy with an appreciable survival benefit. [ABSTRACT FROM AUTHOR]

Background: Intraoperative radiation therapy (IORT) and whole breast irradiation (WBI) are both effective adjuvant radiotherapy methods for ductal carcinoma in situ (DCIS) or early-stage breast cancer (BC) patients undergoing breastconserving surgery (BCS). We aim to evaluate the long-term oncological efficacy and refine patient selection criteria based on our findings. Methods: Female patients who underwent either IORT or WBI from January 2016 to December 2019, with a minimum follow-up of 12 months were collected. IORT was administered as a single fraction of 20 Gray (Gy) to the lumpectomy cavity using the Axxent electronic brachytherapy system, while WBI consisted of a standard fractionation of 50 Gy in 25 fractions, along with a reduced boost of 10 Gy. The clinicopathologic characteristics and oncological outcomes were retrospectively analyzed. Results: A total of 247 patients were enrolled, comprising 164 with BC and 83 with DCIS. Among them, 112 underwent IORT, and 135 received WBI after BCS. The median age was 62.2 years, with median tumor sizes of 1.5 cm for BC and 1.2 cm for DCIS. At a median follow-up of 64.6 months, IORT demonstrated 11 locoregional recurrences (LRR), 1 metastasis, and 1 death, compared to 4 LRR, 5 metastases, and 2 deaths in the WBI group. WBI yielded significantly higher locoregional control (97.0% vs. 90.2%, p = 0.033), although metastasis-free (96.3% vs. 99.1%, p = 0.166) and overall survival rates (98.4% vs. 99%, p = 0.688) did not differ. The LRR rate was significantly higher in the IORT group among the DCIS or BC patients (p = 0.043). The hazard ratio for locoregional recurrence significantly increased in estrogen-receptor-negative (ER-) patients in both univariate analysis (HR = 4.98, 95% CI = 1.76-14.09, p = 0.002) and multivariate analysis (HR = 40.88, 95% CI = 1.29-1297.84, p = 0.035). Additionally, IORT was associated with increased LRR in the multivariate analysis (HR = 4.71, 95% CI = 1.16-19.06, p = 0.030). Conclusion: At a long-term follow-up, the LRR rate was higher in the BCS followed by IORT, without significant differences in metastasis-free or overall survival rates. Our data confirmed the importance of exclusion ER-patients for IORT. [ABSTRACT FROM AUTHOR]

Intraoperative radiation therapy (IORT) has been used in the treatment of locally advanced and recurrent rectal cancers for the last several decades. Given the heterogeneity of patients treated and different indications for use and dosing at different institutions, it has been difficult to discern if IORT adds any appreciable benefit to standard of care therapies. Herein, the rationale for IORT in rectal cancer is discussed along with the most modern and best available data in 2023. IORT is likely indicated in patients with locally advanced and locally recurrent rectal cancer with threatened margins (R0 or R1 resection) to help improve local control. High-quality imaging and multidisciplinary discussion are necessary to ensure optimal patient selection. Appropriate counseling of the patient and excellent team communication are of the utmost importance given the challenging nature of these cases and the prognostic implications of R1 and R2 resections in this patient population. [ABSTRACT FROM AUTHOR]

Background. Breast cancer is the most common cancer in women. The main treatment for breast cancer includes surgery, chemotherapy, radiation therapy, and hormone therapy. The role of radiation therapy in the management of breast cancer continues to evolve. Radiation therapy is currently being de-escalated to include the use of intraoperative radiotherapy (IORT) and adjuvant endocrine therapy. Purpose of the study: to compare the efficacy of IORT with that of external beam radiotherapy (EBRT) in the treatment of early breast cancer. Material and Methods. A retrospective study of 559 patients with early breast cancer was conducted in Clinical Oncology Center of Saint Petersburg. The main treatment group included 273 patients who underwent breast-conserving surgery with IORT and sentinel lymph node biopsy. The control group included 286 patients who underwent breast-conserving surgery with sentinel lymph node biopsy and EBRT. Results. For all patients, the median follow-up time was 59.1 months (interquartile range: 43.7 to 80.7), the minimum follow-up period was 0.6 months, and the maximum follow-up period was 110.4 months. Recurrence occurred in 18 (6.6 %) patients of the main group and in 8 (2.8 %) patients of the control group. A statistically significant association of biological subtype with survival outcomes was found (p=0.02). The hazard ratio for Luminal B of 1.88 (95 % CI 1.02, 3.46) corresponded to a 65 % chance of an earlier onset of a negative outcome. The hazard ratio for triple-negative breast cancer of 3.01 (95 % CI 1.53, 5.95) corresponded to a 75 % chance of an earlier negative outcome. In the main treatment group, 11 (4 %) patients developed disease progression, and 2 of them died of multiple organ failure. In the control group, disease progression was observed in 18 (6.3 %) patients, 6 of whom died. However, the analysis of overall survival using the Kaplan–Meier curve showed a statistically non-significant log-rank p-value (0.73). The 3-year survival rates were 100 % (100 – 100) in the treatment group and 98.2 % (96.7 – 99.8) in the control group. The 5-yaer survival rates were 99.3 % (97.9 – 100) in the treatment group and 97.8 % (96.2 – 99.6) in the control group. These results showed advantage of IORT over EBRT. Conclusions. Intraoperative radiotherapy is a safe and effective alternative to external beam radiotherapy for early breast cancer.

Gallbladder cancer (GBC) is a rare and highly aggressive malignancy, often characterized by nonspecific clinical presentations and late diagnosis, which contribute to its poor prognosis. It is commonly detected at advanced stages, leading to low survival rates. Surgical resection is the primary treatment, with the extent of surgery depending on the T stage of the cancer. In advanced cases, surgery is only considered if it can potentially be curative. Despite various treatment approaches for advanced GBC, survival outcomes remain poor. In our case series, we introduce a novel treatment approach combining cytoreductive surgery, intraoperative radiation therapy, and hyperthermic intraperitoneal chemotherapy. Remarkably, we observed a 100% one-year survival rate, with one patient achieving eight years of disease-free survival without recurrence or metastasis. This aggressive treatment strategy did not lead to increased morbidity or mortality, suggesting its safety and feasibility. However, larger-scale studies are required to draw definitive conclusions. [ABSTRACT FROM AUTHOR]

Background: Intraoperative radiation therapy (IORT), is a promising method which has been widely applied in breast cancer lumpectomy. Although its effect on destructing remaining cancer cells was approved, maintaining or draining post intraoperative radiation therapy wound fluids (PIWF) is challenging. Moreover, the roles of immune cells in interaction with PIWFs have not been studied before which is the main investigation of this paper. Methods: Surgical wound fluids were collected from 24 IDC patients one day after lumpectomy. The patients were divided into control and IORT groups. The collected wound fluids were centrifuged for 20 minutes at 2000 rpm. The concentration of tumor-associated cytokines and inflammasomes were recorded using the immunoassays. Results: PIWFs stimulate the residue of cancer cells in cavity sides causing disease progression. Here we have focused on the effect of PIWFs on the proactivation or deactivation of WBCs in the tumor bed environment. By sequential imaging in time-transient intervals from the interaction between WBCs and cancer cells, PIWFs have no additive proactivating effect on immune cells. Conclusion: PIWFs have significant roles in proliferation of cancer cells but did not show an observable role in pro-activating immune cells against cancer cells. The functions of immune cells did not show any independent proactivation in the presence of PIWFs with respect to their activation in the presence of blood serum. It seems that draining the PIWFs may be required. In future research, we will use tumor samples of the patients instead of cell lines to better investigate the personalized immune-tumor interactions of patients. [ABSTRACT FROM AUTHOR]

Background: Breast-conserving surgery with synchronous 50-kV X-ray intraoperative radiation therapy (TARGIT-IORT) is a convenient form of partial breast irradiation; however, the existing literature supports a wide range of local control rates. Objectives: We investigated the treatment effectiveness and toxic effects of TARGIT-IORT in a patient cohort aged 64 years or older with low-risk breast cancer. Design: Retrospective analysis. Methods: Patients who received breast-conserving surgery with synchronous TARGIT-IORT at a single institution from 2016 to 2019 were reviewed. Additional whole breast irradiation was recommended at the discretion of the treating radiation oncologist. Baseline patient demographics and treatment details were recorded. Acute and chronic toxicities, measured using the Common Terminology Criteria for Adverse Events version 3.0 or 4.0 and breast cosmetic outcomes, using the Harvard Cosmesis score, were recorded. Locoregional recurrence, distant metastasis, and overall survival were recorded, and 5-year rates were estimated using the Kaplan-Meier method. Results: 61 patients were included with a median follow-up of 3.5 years and median age of 72 years. Eight (13%) patients received additional whole breast irradiation, and fifty-four (89%) received adjuvant hormone therapy. There were no local, regional, or distance recurrences. One patient died of complications from COVID-19 infection. Grade 2 + acute and chronic toxicities were observed in 6 (12%) and 7 (14%) patients, respectively. One patient experienced a grade 3 acute toxicity. Cosmetic outcome was "excellent" or "good" in 45 (92%) patients. Conclusions: Breast TARGIT-IORT was well tolerated and conferred excellent disease control in this cohort of patients with low-risk breast cancer. While continued follow-up is required, TARGIT-IORT may be an appropriate treatment option for this population. [ABSTRACT FROM AUTHOR]

Gallbladder cancer (GBC) is a rare and highly aggressive malignancy, often characterized by nonspecific clinical presentations and late diagnosis, which contribute to its poor prognosis. It is commonly detected at advanced stages, leading to low survival rates. Surgical resection is the primary treatment, with the extent of surgery depending on the T stage of the cancer. In advanced cases, surgery is only considered if it can potentially be curative. Despite various treatment approaches for advanced GBC, survival outcomes remain poor. In our case series, we introduce a novel treatment approach combining cytoreductive surgery, intraoperative radiation therapy, and hyperthermic intraperitoneal chemotherapy. Remarkably, we observed a 100% one-year survival rate, with one patient achieving eight years of disease-free survival without recurrence or metastasis. This aggressive treatment strategy did not lead to increased morbidity or mortality, suggesting its safety and feasibility. However, larger-scale studies are required to draw definitive conclusions.

Abstract Intraoperative radiation therapy (IORT) is a radiation technique applying a single fraction with a high dose during surgery. We report the first abdomino-pelvic application of an image-guided intraoperative electron radiation therapy with intraoperative real time dose calculation based on the individual intraoperative patient anatomy. A patient suffering from locoregionally recurrent rectal cancer after treatment with neoadjuvant re-chemoradiation was chosen for this approach. After surgical removal of the recurrence, an adequate IORT applicator was placed as usual. A novel mobile imaging device (ImagingRing, MedPhoton) was positioned around the patient covering the region to be treated with the IORT-applicator in place. It allowed the acquisition of three-dimensional intraoperative cone-beam computed tomography images suitable for dose calculation using an automated scaling (heuristic object and head scatter as well as hardening corrections) of Hounsfield units. After image acquisition confirmed the correct applicator position, the images were transferred to our treatment planning system for intraoperative dose calculation. Treatment could be accomplished using the calculated dose distribution. We herein describe the details of the procedure including necessary adjustments in the typically used IORT equipment and work flow. We further discuss the pros and cons of this new approach generally overcoming a decade long limitation of IORT procedures as well as future perspectives regarding IORT treatments.

Abstract Background/objective Intra-operative radiation therapy (IORT) is a newer partial breast irradiation technique that has been well studied in 2 large randomized trials, the TARGIT-A and ELIOT trials. We initiated our IORT program in 2018 in the context of a registry trial, and aim to report our early results thus far. Methods We instituted an IORT practice using Intrabeam® low energy 50kVp x-rays for selected breast cancer cases in 2018. Patients were enrolled on our institutional registry protocol which allowed for IORT in ER + patients with grade 1–2 DCIS ≤ 2.5 cm or invasive disease ≤ 3.5 cm in patients of at least 45 years of age. Results Between January 2018 and December 2021, 181 patients with clinical stage 0-IIA ER + breast cancer were evaluated. One hundred sixty-seven patients ultimately received IORT to 172 sites. The majority of patients received IORT at the time of initial diagnosis and surgery (160/167; 95.8%). Re-excision post IORT occurred in 16/167 patients (9.6%) due to positive margins. Adjuvant RT to the whole breast +/- LN was ultimately given to 23/167 (13.8%) patients mainly due to positive sentinel LN found on final pathology (12/23; 52%); other reasons were close margins for DCIS (3/23; 13%), tumor size (3/23; 4.3%), and multifactorial (5/23; 17.4%). Five patients (3%) had post-operative complications of wound dehiscence. There were 3 local recurrences (1.6%) at a median follow-up of 27.9 months (range: 0.7– 54.8 months). Conclusions IORT has been proven to be a safe and patient-centered form of local adjuvant RT for our population, in whom compliance with a longer course of external beam radiation can be an issue. Long term efficacy remains to be evaluated through continued follow up. In the era of COVID-19 and beyond, IORT has been an increasingly attractive option, as it greatly minimizes toxicities and patient visits to the clinic. Trial registration All patients were prospectively enrolled on an institutional review board-approved registry trial (IRB number: 2018–9409).

Intraoperative radiation therapy (IORT) is a radiation technique applying a single fraction with a high dose during surgery. We report the first abdomino-pelvic application of an image-guided intraoperative electron radiation therapy with intraoperative real time dose calculation based on the individual intraoperative patient anatomy. A patient suffering from locoregionally recurrent rectal cancer after treatment with neoadjuvant re-chemoradiation was chosen for this approach. After surgical removal of the recurrence, an adequate IORT applicator was placed as usual. A novel mobile imaging device (ImagingRing, MedPhoton) was positioned around the patient covering the region to be treated with the IORT-applicator in place. It allowed the acquisition of three-dimensional intraoperative cone-beam computed tomography images suitable for dose calculation using an automated scaling (heuristic object and head scatter as well as hardening corrections) of Hounsfield units. After image acquisition confirmed the correct applicator position, the images were transferred to our treatment planning system for intraoperative dose calculation. Treatment could be accomplished using the calculated dose distribution. We herein describe the details of the procedure including necessary adjustments in the typically used IORT equipment and work flow. We further discuss the pros and cons of this new approach generally overcoming a decade long limitation of IORT procedures as well as future perspectives regarding IORT treatments. [ABSTRACT FROM AUTHOR]

Purpose: Portal vein and superior mesenteric vein thrombosis (PVT/SMVT) are potentially morbid complications of radiation dose–escalated local therapy for pancreatic cancer. We retrospectively reviewed records for patients treated with and without intraoperative radiation (IORT) to identify risk factors for PVT/SMVT. Methods: Ninety-six patients with locally advanced or borderline resectable pancreatic adenocarcinoma received neoadjuvant therapy followed by surgical exploration from 2009 to 2014. Patients at risk for close or positive surgical margins received IORT boost to a biologically effective dose (BED10) > 100. Prognostic factors for PVT/SMVT were evaluated using competing risks regression. Results: Median follow-up was 79 months for surviving patients. Fifty-six patients (58%) received IORT. Twenty-nine patients (30%) developed PVT/SMVT at a median time of 18 months. On univariate competing risks regression, operative blood loss and venous repair with a vascular interposition graft, but not IORT dose escalation or diabetes history, were significantly associated with PVT/SMVT. The development of thrombosis in the absence of recurrence was significantly associated with a longstanding diabetes history, post-neoadjuvant treatment CA19-9, and operative blood loss. All 4 patients who underwent both IORT and vascular repair with a graft developed PVT/SMVT. PVT/SMVT in the absence of recurrence is not associated with significantly worsened overall survival but led to frequent medical interventions. Conclusions: Approximately 30% of patients who underwent neoadjuvant chemoradiation for PDAC developed PVT/SMVT a median of 18 months following surgery. This was significantly associated with venous reconstruction with vascular grafts, but not with escalating radiation dose. PVT/SMVT in the absence of recurrence was associated with significant morbidity. [ABSTRACT FROM AUTHOR]

External boost radiotherapy (EBRT) and intraoperative radiotherapy (IORT) are shown to be effective in patients with early-stage breast cancer. However, the difference between IORT and EBRT for patients' prognosis remains to be elucidated. The purpose of this meta-analysis is to investigate differences in local recurrence (LR), distant metastases, disease free survival (DFS), and overall survival (OS) between these two therapies. We searched the Cochrane Library, PubMed, Web of Science and Embase, from inception to Jan 10th, 2022. We used The Cochrane risk-of-bias assessment tool to assess the risk of bias of the included studies, and the STATA15.0 tool was used for the meta-analyses. Eight studies were ultimately included. Meta-analysis demonstrated that there was an inconsistent finding in the long-term risk of LR between the two radiotherapies, and there was no significant difference in short-term risk of LR, the metastasis rate, DFS, and OS IORT would be more convenient, less time-consuming, less costly, and more effective at reducing side effects and toxicity. However, these benefits must be balanced against the potential for increased risk of LR in the long term. [ABSTRACT FROM AUTHOR]

Purpose of Review: Following breast-conserving surgery, adjuvant radiation has traditionally been delivered using whole breast irradiation (WBI). Over the past several decades, multiple studies have evaluated the role of smaller target volumes for adjuvant radiation therapy delivered with partial breast irradiation (PBI) or intraoperative radiation therapy (IORT) techniques. The intent of this review is to provide an update on the role of PBI and IORT given recently published studies. Recent Findings: Multiple randomized trials evaluating PBI have been published with mature outcomes, demonstrating comparable rates of local recurrence to WBI at 10 years. IORT has been shown to have increased rates of local recurrence in the ELIOT and TARGIT-A trials; unfortunately, the TARGIT-A study has failed to provide long-term outcomes for all IORT patients together or long-term rates of local recurrence (only local recurrence-free survival). Summary: Data support utilization of PBI for women diagnosed with early-stage breast cancer following breast-conserving surgery. In contrast, IORT studies have demonstrated elevated rates of local recurrence and should not be utilized outside of prospective studies. [ABSTRACT FROM AUTHOR]

Background/objective: Intra-operative radiation therapy (IORT) is a newer partial breast irradiation technique that has been well studied in 2 large randomized trials, the TARGIT-A and ELIOT trials. We initiated our IORT program in 2018 in the context of a registry trial, and aim to report our early results thus far. Methods: We instituted an IORT practice using Intrabeam® low energy 50kVp x-rays for selected breast cancer cases in 2018. Patients were enrolled on our institutional registry protocol which allowed for IORT in ER + patients with grade 1–2 DCIS ≤ 2.5 cm or invasive disease ≤ 3.5 cm in patients of at least 45 years of age. Results: Between January 2018 and December 2021, 181 patients with clinical stage 0-IIA ER + breast cancer were evaluated. One hundred sixty-seven patients ultimately received IORT to 172 sites. The majority of patients received IORT at the time of initial diagnosis and surgery (160/167; 95.8%). Re-excision post IORT occurred in 16/167 patients (9.6%) due to positive margins. Adjuvant RT to the whole breast +/- LN was ultimately given to 23/167 (13.8%) patients mainly due to positive sentinel LN found on final pathology (12/23; 52%); other reasons were close margins for DCIS (3/23; 13%), tumor size (3/23; 4.3%), and multifactorial (5/23; 17.4%). Five patients (3%) had post-operative complications of wound dehiscence. There were 3 local recurrences (1.6%) at a median follow-up of 27.9 months (range: 0.7– 54.8 months). Conclusions: IORT has been proven to be a safe and patient-centered form of local adjuvant RT for our population, in whom compliance with a longer course of external beam radiation can be an issue. Long term efficacy remains to be evaluated through continued follow up. In the era of COVID-19 and beyond, IORT has been an increasingly attractive option, as it greatly minimizes toxicities and patient visits to the clinic. Trial registration: All patients were prospectively enrolled on an institutional review board-approved registry trial (IRB number: 2018–9409). [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases are of increasing concern in the management of cancer patients. New systemic treatment options like specific targeting agents or immune checkpoint inhibitors allow for longer survival with a higher incidence of brain metastases over the course of the disease. Single or a few small, asymptomatic lesions are mainly treated with focal stereotactic radiotherapy. On the other hand, in many cases, large and, in particular, symptomatic metastases require microsurgical resection for immediate symptom relief. However, the indication for surgery can be challenging concerning the clinic, patient and tumor characteristics, and the availability of alternative conservative treatment options. Of note, with surgery alone, local recurrence rates are about 50%; therefore, additional RT is needed to improve outcomes. Postsurgical radiotherapy (RT) has been early proven to prevent local tumor recurrence, initially performed with whole brain RT (WBRT). Subsequent to disadvantageous cognitive sequalae for the patient and the broad distribution of modern linear accelerators, focal irradiation of the tumor has omitted WBRT in most cases. In many studies, the effectiveness of local RT of the resection cavity, either as single-fraction stereotactic radiosurgery (SRS) or hypo-fractionated stereotactic RT (hFSRT), has been demonstrated to be effective and safe. However, whereas prospective high-level incidence is still lacking on which dose and fractionation scheme is the best choice for the patient, further ablative techniques have come into play. Neoadjuvant SRS (N-SRS) prior to resection combines straightforward target delineation with an accelerated post-surgical phase, allowing an earlier start of systemic treatment or rehabilitation as indicated. In addition, low-energy intraoperative RT (IORT) on the surgical bed has been introduced as another alternative to external beam RT, offering sterilization of the cavity surface with steep dose gradients towards the healthy brain. This consensus paper summarizes current local treatment strategies for resectable brain metastases regarding available data and patient-centered decision-making. [ABSTRACT FROM AUTHOR]

Abstract Background Localized pancreatic adenocarcinoma carries a poor prognosis even after aggressive therapy. Up to 40% of patients may develop locoregional disease as the first site of failure. As such, there may be a role for intensification of local therapy such as radiation therapy. Radiation dose escalation for pancreatic cancer is limited by proximity of the tumor to the duodenum. However, the duodenum is removed during Whipple procedure, allowing the opportunity to dose escalate with intraoperative radiation therapy (IORT). Although prior studies have shown potential benefit of IORT in pancreatic cancer, these studies did not utilize ablative doses (biologically effective dose [BED10] > 100 Gy). Furthermore, the optimal radiation target volume in this setting is unclear. There has been increased interest in a “Triangle Volume” (TV), bordered by the celiac axis, superior mesenteric artery, common hepatic artery, portal vein, and superior mesenteric vein. Dissection of this area, has been advocated for by surgeons from Heidelberg as it contains extra-pancreatic perineural and lymphatic tracts, which may harbor microscopic disease at risk of mediating local failure. Interestingly, a recent analysis from our institution indicated that nearly all local failures occur in the TV. Therefore, the purpose of this protocol is to evaluate the safety of delivering an ablative radiation dose to the TV with IORT following neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT). Methods Patients with non-metastatic pancreatic adenocarcinoma centered in the head or neck of the pancreas will be enrolled. Following treatment with multi-agent neoadjuvant chemotherapy, patients will undergo SBRT (40 Gy/5 fractions) followed by IORT (15 Gy/1 fraction) to the TV during the Whipple procedure. The primary objective is acute ( 90 days) toxicity after IORT measured by Clavien-Dindo classification, overall survival, local progression-free survival, distant metastasis-free survival, and progression-free survival. Discussion If the results show that delivering an ablative radiation dose to the TV with IORT after neoadjuvant chemotherapy and SBRT is safe and feasible, it warrants further investigation in a phase II trial to evaluate efficacy of this approach. Trial Registration This study was registered at ClinicalTrials.gov on 12/2/2021 (NCT05141513). https://clinicaltrials.gov/ct2/show/NCT05141513

Background. Comprehensive treatment of breast cancer includes surgery, radiation therapy and systemic treatment. Radiation therapy plays an integral role in the treatment of early breast cancer. The appointment of a targeted dose of radiation to the bed of the primary tumor reduces the risk of local recurrence.Objective: to evaluate the effectiveness of intraoperative radiation therapy in the treatment of early breast cancer.Materials and methods. A retrospective study was conducted on the basis of the St. Petersburg City Clinical Oncology Center. Patients with organ-preserving surgery and intraoperative radiation therapy were selected. Of the 352 patients, 273 patients met the inclusion/non-inclusion criteria. Inclusion criteria were verified breast cancer, clinical stage I–IIA, tumor size no more than 3 cm, absence of visible axillary lymph nodes and monocentric nature of tumor growth. All patients underwent sectoral resection of the mammary gland with a biopsy of the sentinel lymph nodes and intraoperative radiation therapy.Results. The mean age of the patients was 59 years. For 273 patients, the median follow-up was 59.1 months. During this period, 18 (6.6 %) local recurrences of the disease were noted, of which 7 (39 %) patients with luminal A, 6 (33 %) patients with luminal B, 1 (6 %) patient with luminal B HER2/neu 3+, and 4 (22 %) patients with triple negative breast cancer. Within 3 years of follow-up, recurrence-free survival was 98.5 %, within 5 years – 96.4 %.Conclusion. The use of intraoperative radiation therapy for early breast cancer is an effective and safe treatment method.

Precision breast intraoperative radiation therapy (PB-IORT) incorporates computed tomography–guided treatment planning and high dose rate brachytherapy to deliver a single dose of highly conformal radiational therapy. The purpose of this study is to determine factors associated with poor cosmetic outcomes after treatment with PB-IORT. The study included all consecutive participants enrolled in an ongoing phase II clinical trial that had completed a minimum of 12 mo of follow-up. A poor cosmetic outcome was defined as scoring "fair" or "poor" on the Harvard Cosmesis evaluation, or "some" or "very much" on any of the three general cosmesis categories. Statistical analysis was performed utilizing R. The final cohort included 201 participants, of which 181 (90%) had an overall good/excellent cosmetic outcome. Group 1 consisted of 162 (81%) participants who reported only excellent/good cosmetic outcomes. Group 2 consisted of 39 (19%) participants who reported some aspect of a poor cosmetic outcome. On multivariable analysis, participants with ductal carcinoma in situ were significantly more likely to experience a poor cosmetic outcome (odds ratio 2.45, 95% confidence interval 1.03-5.82, P = 0.04), and those who received subsequent whole breast irradiation were also more likely to have a poor cosmetic outcome (odds ratio 10.20, 95% confidence interval CI 1.04-99.95, P = 0.04). Patients with need for further radiation after PB-IORT are at increased risk for a poor cosmetic outcome. Larger balloon volume and distance between the skin do not have deleterious effects on cosmetic outcomes. [ABSTRACT FROM AUTHOR]

Background: Peritoneal sarcomatosis (PS) is an aggressive disease; cytoreductive surgery (CRS) could be curative. Aim: Can the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) +/- intraoperative radiation therapy (IORT) overcome treatment failure with an overall survival benefit. Methods: Retrospective review of the medical records of patients with PS treated by CRS, HIPEC and IORT at a comprehensive cancer center in the period between 2011-2016. Results: Twenty-four patients were identified. Fifteen were men and their median age was 58 years. Liposarcoma was the most frequent diagnosis (50%). Cytoreduction completeness (CC) score 0/1 was achieved in 19 patients, with a median pathological peritoneal cancer index (pPCI) of 12. Intraoperative radiation therapy was given in 16 patients. Eight patients developed grade III-IV Clavien-Dindo post-operative complications and 1 patient died 5 days post operative. Adjuvant chemotherapy was received in 9 patients. After a median follow-up of 28.5 months, the median PFS was 20.7 months, while the estimated 2- and 4-year PFS were 37.1% and 19.1%, respectively. The median OS was 176.5 months and the estimated 2- and 4-year OS were 95.8% and 79.8%, respectively. In the univariate analysis, the PFS differed significantly according to the CC score only. The median PFS for patients with CC 0-1 was 23.8 vs. 8.8 months for those with CC 2-3 (p = 0.027). Conclusions: The addition of HIPEC and IORT to CRS in the management of PS is feasible and safe. Comparing our results to several studies, this multimodality approach seems to improve local and regional control rates. A larger cohort of patients is needed for further evaluation and to give a concrete conclusion.

Background: Local cancer therapy by combining real-time surgical exploration and resection with delivery of a single dose of high-energy electron irradiation entails a very precise and effective local therapeutic approach. Integrating the benefits from minimally invasive surgical techniques with the very precise delivery of intraoperative electron irradiation results in an efficient combined modality therapy. Methods: Patients with locally advanced disease, who are candidates for laparoscopic and/or thoracoscopic surgery, received an integrated multimodal management. Preoperative treatment included induction chemotherapy and/or chemoradiation, followed by laparoscopic surgery and intraoperative electron radiation therapy. Results: In a period of 5 consecutive years, 125 rectal cancer patients were treated, of which 35% underwent a laparoscopic approach. We found no differences in cancer outcomes and tolerance between the open and laparoscopic groups. Two esophageal cancer patients were treated with IOeRT during thoracoscopic resection, with the resection specimens showing intense downstaging effects. Two oligo-recurrent prostatic cancer patients (isolated nodal progression) had a robotic-assisted surgical resection and post-lymphadenectomy electron boost on the vascular and lateral pelvic wall. Conclusions: Minimally invasive and robotic-assisted surgery is feasible to combine with intraoperative electron radiation therapy and offers a new model explored with electron-FLASH beams. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in systemic cancer management have improved survival for numerous types of solid cancer; therefore, the number of patients harboring BM is increasing. According to established guidelines, resection should be carried out in patients with single brain metastases and controlled primary disease or when histopathologic diagnosis is crucial for decision-making in cancer management. Post-surgery rates of local recurrence are high; hence, adjuvant local radiation therapy (RT) is indicated to improve outcomes. So far, there is no standard of care regarding dose and fractionation; furthermore, delineation of the cavity can be challenging. Lately, low-energy X-ray intraoperative radiation therapy (IORT) applied to the resection bed has emerged in clinical practice, offering local ablative treatment with steep dose gradients towards the surrounding healthy brain. We here retrospectively describe 18 patients with resected brain metastases, which had undergone IORT, demonstrating the effectiveness and safety of this technique in accordance with previous studies. Background: Resection followed by local radiation therapy (RT) is the standard of care for symptomatic brain metastases. However, the optimal technique, fractionation scheme and dose are still being debated. Lately, low-energy X-ray intraoperative RT (lex-IORT) has been of increasing interest. Method: Eighteen consecutive patients undergoing BM resection followed by immediate lex-IORT with 16–30 Gy applied to the spherical applicator were retrospectively analyzed. Demographic, RT-specific, radiographic and clinical data were reviewed to evaluate the effectiveness and safety of IORT for BM. Descriptive statistics and Kaplan–Meyer analysis were applied. Results: The mean follow-up time was 10.8 months (range, 0–39 months). The estimated local control (LC), distant brain control (DBC) and overall survival (OS) at 12 months post IORT were 92.9% (95%-CI 79.3–100%), 71.4% (95%-CI 50.2–92.6%) and 58.0% (95%-CI 34.1–81.9%), respectively. Two patients developed radiation necrosis (11.1%) and wound infection (CTCAE grade III); both had additional adjuvant treatment after IORT. For five patients (27.8%), the time to the start or continuation of systemic treatment was ≤15 days and hence shorter than wound healing and adjuvant RT would have required. Conclusion: In accordance with previous series, this study demonstrates the effectiveness and safety of IORT in the management of brain metastases despite the small cohort and the retrospective characteristic of this analysis. [ABSTRACT FROM AUTHOR]

Second primary cancers and locoregional recurrences in head and neck cancers are common. Management is challenging owing to the effects of previous treatment. Locoregional therapy, whenever feasible, offers possibility of cure. We have managed a patient who has over a period of 15 years been treated seven times. Treatment included surgical resection four times, flap reconstruction thrice, postoperative radiation thrice, radiation therapy alone thrice. Brachytherapy has been used in two instances, intraoperative brachytherapy once and surface mould application once. Patient has maintained a good quality of life during these fifteen years but suffers from xerostomia and nasogastric tube dependence at present. The management of this patient teaches us important lessons in terms of using modern surgery and advances in radiation therapy for achieving good patient benefit. [ABSTRACT FROM AUTHOR]

This article discusses the experience of using intraoperative radiation therapy in the treatment of patients with breast cancer, as well as the prospects for the development of this area in terms of benefits (improved therapy effect, reduced severity of side effects, no effect on adjacent organs) and risks (the possibility of local recurrence) for patients.

Abstract Background and objective We report our experiences with Intraoperative radiation therapy (IORT) among breast cancer (BC) patients in our region. Methods All patients who received radical IORT from April 2014 on to March 2020 were included in the study. Patient selection criteria included: Age equal or older than 45 years old; All cases of invasive carcinomas (in cases of lobular carcinomas only with MRI and confirmation); Patients who were 45–50 years old with a tumor size of 0–2 cm, 50–55 years old with a tumor size of

Background: Localized pancreatic adenocarcinoma carries a poor prognosis even after aggressive therapy. Up to 40% of patients may develop locoregional disease as the first site of failure. As such, there may be a role for intensification of local therapy such as radiation therapy. Radiation dose escalation for pancreatic cancer is limited by proximity of the tumor to the duodenum. However, the duodenum is removed during Whipple procedure, allowing the opportunity to dose escalate with intraoperative radiation therapy (IORT). Although prior studies have shown potential benefit of IORT in pancreatic cancer, these studies did not utilize ablative doses (biologically effective dose [BED10] > 100 Gy). Furthermore, the optimal radiation target volume in this setting is unclear. There has been increased interest in a "Triangle Volume" (TV), bordered by the celiac axis, superior mesenteric artery, common hepatic artery, portal vein, and superior mesenteric vein. Dissection of this area, has been advocated for by surgeons from Heidelberg as it contains extra-pancreatic perineural and lymphatic tracts, which may harbor microscopic disease at risk of mediating local failure. Interestingly, a recent analysis from our institution indicated that nearly all local failures occur in the TV. Therefore, the purpose of this protocol is to evaluate the safety of delivering an ablative radiation dose to the TV with IORT following neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT).Methods: Patients with non-metastatic pancreatic adenocarcinoma centered in the head or neck of the pancreas will be enrolled. Following treatment with multi-agent neoadjuvant chemotherapy, patients will undergo SBRT (40 Gy/5 fractions) followed by IORT (15 Gy/1 fraction) to the TV during the Whipple procedure. The primary objective is acute (< 90 days) toxicity after IORT measured by Clavien-Dindo classification. Secondary objectives include late (> 90 days) toxicity after IORT measured by Clavien-Dindo classification, overall survival, local progression-free survival, distant metastasis-free survival, and progression-free survival.Discussion: If the results show that delivering an ablative radiation dose to the TV with IORT after neoadjuvant chemotherapy and SBRT is safe and feasible, it warrants further investigation in a phase II trial to evaluate efficacy of this approach. Trial Registration This study was registered at ClinicalTrials.gov on 12/2/2021 (NCT05141513). https://clinicaltrials.gov/ct2/show/NCT05141513. [ABSTRACT FROM AUTHOR]

Background: Salvage surgery is considered an option for isolated recurrences of retroperitoneal and pelvic tumors, in patients who have undergone previous radiotherapy. In order to increase local control intra operative electron radiation therapy (IOERT) can be used in these patients to administer additional radiation dose. We evaluated the outcomes and adverse effects in patients with retroperitoneal sarcoma and gynecologic tumors after salvage surgery and IOERT. Materials and Methods: Twenty patients were retrospectively analyzed. Twenty-three IOERT treatments were performed after surgery. six (30%) were sarcoma and 14 (70%) were gynecological carcinoma. Administered dose depended on previous dose received with external beam radiotherapy (EBRT) and proximity to critical structures. The toxicities were scored using the Common Terminology Criteria for Adverse events version 4.0. Results: The median age of the patients was 51 years (range 34-70). After a median follow-up of 32 months (range 1-68), in the sarcoma group the local control rate was 66.6%; while in the gynecological group the local control rate was 64.3%. In relation to late toxicity, one patient had a Grade 2 vesicovaginal fistula, and one patient presented Grade 4 enterocolitis and enteric intestinal fistula. conclusions: IOERT could have a role in the treatment of retroperitoneal sarcomas in primary tumors after EBRT, as it may suggest a benefit in local control or recurrences after surgical resection in those at high risk of microscopic residual disease. The addition of IOERT to salvage resection for isolated recurrence of gynecologic cancers suggest favorable local control in cases with concern for residual microscopic disease. [ABSTRACT FROM AUTHOR]

Background: Intraoperative radiation therapy (IORT) and whole breast irradiation (WBI) are both effective adjuvant radiotherapy methods for ductal carcinoma in situ (DCIS) or early-stage breast cancer (BC) patients undergoing breast-conserving surgery (BCS). We aim to evaluate the long-term oncological efficacy and refine patient selection criteria based on our findings., Methods: Female patients who underwent either IORT or WBI from January 2016 to December 2019, with a minimum follow-up of 12 months were collected. IORT was administered as a single fraction of 20 Gray (Gy) to the lumpectomy cavity using the Axxent electronic brachytherapy system, while WBI consisted of a standard fractionation of 50 Gy in 25 fractions, along with a reduced boost of 10 Gy. The clinicopathologic characteristics and oncological outcomes were retrospectively analyzed., Results: A total of 247 patients were enrolled, comprising 164 with BC and 83 with DCIS. Among them, 112 underwent IORT, and 135 received WBI after BCS. The median age was 62.2 years, with median tumor sizes of 1.5 cm for BC and 1.2 cm for DCIS. At a median follow-up of 64.6 months, IORT demonstrated 11 locoregional recurrences (LRR), 1 metastasis, and 1 death, compared to 4 LRR, 5 metastases, and 2 deaths in the WBI group. WBI yielded significantly higher locoregional control (97.0% vs. 90.2%, p = 0.033), although metastasis-free (96.3% vs. 99.1%, p = 0.166) and overall survival rates (98.4% vs. 99%, p = 0.688) did not differ. The LRR rate was significantly higher in the IORT group among the DCIS or BC patients (p = 0.043). The hazard ratio for locoregional recurrence significantly increased in estrogen-receptor-negative (ER-) patients in both univariate analysis (HR = 4.98, 95% CI = 1.76-14.09, p = 0.002) and multivariate analysis (HR = 40.88, 95% CI = 1.29-1297.84, p = 0.035). Additionally, IORT was associated with increased LRR in the multivariate analysis (HR = 4.71, 95% CI = 1.16-19.06, p = 0.030)., Conclusion: At a long-term follow-up, the LRR rate was higher in the BCS followed by IORT, without significant differences in metastasis-free or overall survival rates. Our data confirmed the importance of exclusion ER- patients for IORT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chi, Ko, Yang, Liu, Chi and Cheng.)

Background and Objectives: The aim of this study was to look at the overall survival (OS), progression-free survival (PFS), and prognostic factors associated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with intraoperative radiation therapy (IORT)., Methods: This study is a single center retrospective study performed on 159 patients who underwent treatment with CRS and HIPEC combined with IORT for abdominopelvic malignancies. OS and PFS were used to evaluate the efficacy of this treatment strategy amongst patients with abdominopelvic malignancies., Results: The cohort's median age was 53 years, with a male predominance (58.5%). The median OS was not reached, but the mean OS was 76.87 months. In univariate analysis, several factors, including synchronous organ metastasis, Pathologic Peritoneal Carcinomatosis Index (pPCI) ≥10, increased estimated blood loss, and severe postoperative complications, were associated with worse OS. However, multivariate analysis identified pPCI ≥ 10 as the sole independent predictor of worse OS. The 1- and 3-year survival rates were 83% and 70.4%, respectively. pPCI ≥ 10 and severe postoperative complications were significant predictors of worse survival outcomes., Conclusions: Radical surgery alone is not enough, and CRS combined with HIPEC and IORT, when indicated, was proven to be safe and effective with no added morbidity or mortality., (© 2024 Wiley Periodicals LLC.)

Abstract Background Pancreatic cancer has highly aggressive features, such as local recurrence that leads to significantly high morbidity and mortality and recurrence after successful tumour resection. Intraoperative radiation therapy (IORT), which delivers targeted radiation to a tumour bed, is known to reduce local recurrence by directly killing tumour cells and modifying the tumour microenvironment. Methods Among 30 patients diagnosed with pancreatic cancer, 17 patients received IORT immediately after surgical resection. We investigated changes in the immune response induced by IORT by analysing the peritoneal fluid (PF) and blood of patients with and without IORT treatment after pancreatic cancer surgery. Further, we treated three pancreatic cell lines with PF to observe proliferation and activity changes. Results Levels of cytokines involved in the PI3K/SMAD pathway were increased in the PF of IORT-treated patients. Moreover, IORT-treated PF inhibited the growth, migration, and invasiveness of pancreatic cancer cells. Changes in lymphocyte populations in the blood of IORT-treated patients indicated an increased immune response. Conclusions Based on the characterisation and quantification of immune cells in the blood and cytokine levels in the PF, we conclude that IORT induced an anti-tumour effect by activating the immune response, which may prevent pancreatic cancer recurrence. Clinical trial registration NCT03273374 .

Background: Peritoneal sarcomatosis (PS) is an aggressive disease; cytoreductive surgery (CRS) could be curative. Aim: Can the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) +/- intraoperative radiation therapy (IORT) overcome treatment failure with an overall survival benefit. Methods: Retrospective review of the medical records of patients with PS treated by CRS, HIPEC and IORT at a comprehensive cancer center in the period between 2011-2016. Results: Twenty-four patients were identified. Fifteen were men and their median age was 58 years. Liposarcoma was the most frequent diagnosis (50%). Cytoreduction completeness (CC) score 0/1 was achieved in 19 patients, with a median pathological peritoneal cancer index (pPCI) of 12. Intraoperative radiation therapy was given in 16 patients. Eight patients developed grade III-IV Clavien-Dindo post-operative complications and 1 patient died 5 days post operative. Adjuvant chemotherapy was received in 9 patients. After a median follow-up of 28.5 months, the median PFS was 20.7 months, while the estimated 2- and 4-year PFS were 37.1% and 19.1%, respectively. The median OS was 176.5 months and the estimated 2- and 4-year OS were 95.8% and 79.8%, respectively. In the univariate analysis, the PFS differed significantly according to the CC score only. The median PFS for patients with CC 0-1 was 23.8 vs. 8.8 months for those with CC 2-3 (p = 0.027). Conclusions: The addition of HIPEC and IORT to CRS in the management of PS is feasible and safe. Comparing our results to several studies, this multimodality approach seems to improve local and regional control rates. A larger cohort of patients is needed for further evaluation and to give a concrete conclusion. [ABSTRACT FROM AUTHOR]

Precision breast intraoperative radiation therapy (PB -IORT) is a novel approach to adjuvant radiation therapy for early-stage breast cancer performed as part of a phase II clinical trial at two institutions. One institution performs the entire procedure in an integrated brachytherapy suite which contains a CT-on-rails imaging unit and full anesthesia capabilities. At the other, breast conserving surgery and radiation therapy take place in two separate locations. Here, we utilize time-driven activity-based costing (TDABC) to compare these two models for the delivery of PB-IORT. Process maps were created to describe each step required to deliver PB -IORT at each institution, including personnel, equipment, and supplies. Time investment was estimated for each step. The capacity cost rate was determined for each resource, and total costs of care were then calculated by multiplying the capacity cost rates by the time estimate for the process step and adding any additional product costs. PB -IORT costs less to deliver at a distributed facility, as is more commonly available, than an integrated brachytherapy suite ($3,262.22 vs. $3,996.01). The largest source of costs in both settings ($2,400) was consumable supplies, including the brachytherapy balloon applicator. The difference in costs for the two facility types was driven by personnel costs ($1,263.41 vs. $764.89). In the integrated facility, increased time required by radiation oncology nursing and the anesthesia attending translated to the greatest increases in cost. Equipment costs were also slightly higher in the integrated suite setting ($332.60 vs. $97.33). The overall cost of care is higher when utilizing an integrated brachytherapy suite to deliver PB- IORT. This was primarily driven by additional personnel costs from nursing and anesthesia, although the greatest cost of delivery in both settings was the disposable brachytherapy applicator. These differences in cost must be balanced against the potential impact on patient experience with these approaches. [ABSTRACT FROM AUTHOR]

: To investigate patient-perceived quality of life (QOL) among patients treated with a novel form of breast intraoperative radiation therapy (PB-IORT). : Patients treated with PB-IORT as part of a phase II clinical trial from 2013 to 2020 were identified. Patients were given the European Organization for Research and Treatment of Cancer (EORTC) core 30-item Quality of Life Questionnaire (QLQ-C30) encompassing global health, functionality, and symptomatology at baseline, 1-month, 6-months, 12-months, and 24-months after PB-IORT. Scores were on a 100-point scale with change greater than 10 considered clinically significant. Scores at interval follow-up were compared to baseline using repeated measure modeling with an unstructured covariance matrix. : The cohort consisted of 303 patients, a majority of which were White (84.2%) with a median age of 64 years (IQR: 52, 76). One month after PB-IORT, a decline from baseline in physical (-2.5, 95% CI: -4.4 - -0.55, p = 0.01), role (-7.6, 95% CI: -11.7 - -3.5, p < 0.001), and social functioning (-3.0, 95% CI: -5.5 - -0.42, p = 0.02) were observed, which correlated with increased fatigue (8.4, 95% CI: 5.5–11.3, p < 0.001). At 6 months, nearly all QOL measures returned to baseline or improved. There were no statistically or clinically significant differences from baseline in overall global health. All functional and symptom scale differences were less than 10, indicating minimal clinical significance. : PB-IORT has minimal negative impact on QOL, further supporting this patient-centered treatment approach for early-stage breast cancer. [ABSTRACT FROM AUTHOR]

Background: To investigate dose distribution of the 5cm spherical applicator of the INTRABEAM™ intraoperative radiation therapy (IORT) device via thermoluminescence dosimeters (TLDs) and Radiographic films. Independent dose distribution assessment of IORT devices is considered important. Several methods are described for this purpose, including TLDs and films. However, Radiographic films are not routinely used. Materials and methods: Twenty TLDs were used for depth dose measuring and evaluating the isotropy in water. Additionally, the isotropy was assessed separately via Radiographic films in air by drawing isodose curves. Results: TLD measurements showed a steep dose decline which the relative average dose of 0.94 at the applicator surface reduced to 0.32, 0.13, and 0.07 at 1, 2, and 3 cm depths in water, respectively. Some remarkable isodose curves prepared using Radiographic films showed forward anisotropy of the 5 cm applicator. Conclusion: A very steep dose decline and approximately isotropic dose distribution of the 5 cm applicator were observed via TLD measurements. Radiographic films showed acceptable potential for drawing dose distribution maps. However, they should be applied in more various radiation setups to be implemented more confidently. [ABSTRACT FROM AUTHOR]

Simple Summary: Intraoperative electron radiation therapy (IOERT) has repeatedly demonstrated its power to yield high local control rates in all risk constellation of patients with invasive breast cancer when given as tumor bed boost prior to conventional whole breast irradiation (WBI) after breast conserving surgery (BCS). Since the standard for WBI continuously moved towards hypofractionation, we initiated a prospective trial in 2011 where we combined a high precision IOERT boost with a "moderate" hypofractionation schedule (15 × 2.7 Gy), the HIOB-trial [NCT01343459], as clinical evidence for this combination was scarce. Our results demonstrated a low five-year local recurrence rate (overall two events in a population of 1119 patients), which undershot such best evidences in two age groups (41–50 y and >50 y). As acute and late toxicity were mild with no impaired cosmetic outcome, the HIOB-concept seems to be a viable treatment option for patients who underwent BCS and intended WBI. Background and purpose: To investigate intraoperative electron radiation therapy (IOERT) as a tumor bed boost during breast conserving surgery (BCS) followed by hypofractionated whole breast irradiation (HWBI) on age-correlated in-breast recurrence (IBR) rates in patients with low- to high-risk invasive breast cancer. Material and methods: BCS and IOERT (11.1 Gy) preceded a HWBI (40.5 Gy) in 15 fractions. Five-year IBR-rates were compared by a sequential ratio test (SQRT) with best evidences in three age groups (35–40 y and 41–50 y: 3.6%, >50 y: 2%) in a prospective single arm design. Null hypothesis (H0) was defined to undershoot these benchmarks for proof of superiority. Results: Of 1445 enrolled patients, 326 met exclusion criteria, leaving 1119 as eligible for analysis. After a median follow-up of 50 months (range 0.7–104), we detected two local recurrences, both in the age group >50 y. With no observed IBR, superiority was demonstrated for the patient groups 41–50 and >50 y, respectively. For the youngest group (35–40 y), no appropriate statistical evaluation was yet possible due to insufficient recruitment. Conclusions: In terms of five-year IBR-rates, Boost-IOERT followed by HWBI has been demonstrated to be superior in patients older than 50 and in the age group 41–50 when compared to best published evidence until 2010. [ABSTRACT FROM AUTHOR]

Background and Objective: We report our experiences with Intraoperative radiation therapy (IORT) among breast cancer (BC) patients in our region.Methods: All patients who received radical IORT from April 2014 on to March 2020 were included in the study. Patient selection criteria included: Age equal or older than 45 years old; All cases of invasive carcinomas (in cases of lobular carcinomas only with MRI and confirmation); Patients who were 45-50 years old with a tumor size of 0-2 cm, 50-55 years old with a tumor size of < 2.5 cm, and those who were ≥ 55 years old with a tumor size of < 3 cm; Invasive tumors only with a negative margin; Negative nodal status (exception in patients with micrometastasis); A positive estrogen receptor status. Primary endpoints included death and recurrence which were assessed using the Kaplan-Meier method.Results: Overall, 252 patients entered the study. Mean (SD) age of patients was 56.43 ± 7.79 years. In total, 32.9% of patients had a family history of BC. Mean (SD) tumor size was 1.56 ± 0.55 cm. Mean (IQR) follow-up of patients was 36.3 ± 18.7 months. Overall, 8 patients (3.1%) experienced recurrence in follow-up visits (disease-free-survival of 96.1%), among which four (1.5%) were local recurrence, two (0.8%) were regional recurrence and two patients (0.8%) had metastasis. Median (IQR) time to recurrence was 46 (22, 53.7) months among the eight patient who had recurrence. Overall, one patient died due to metastasis in our series. Eleven patients (4.3%) with DCIS in our study received IORT. All these patients had free margins in histopathology examination and none experienced recurrence.Conclusion: Inhere we reported our experience with the use of IORT in a region where facilities for IORT are limited using our modified criteria for patient selection. [ABSTRACT FROM AUTHOR]

Purpose: The INTRABEAM system is a miniature accelerator for low‐energy X‐ray Intra‐Operative Radiation Therapy (IORT), and it could benefit from a fast and accurate dose computation tool. With regards to accuracy, dose computed with Monte Carlo (MC) simulations are the gold standard, however, they require a large computational effort and consequently they are not suitable for real‐time dose planning. This work presents a comparison of the implementation on Graphics Processing Unit (GPU) of two different dose calculation algorithms based on MC phase‐space (PHSP) information to compute dose distributions for the INTRABEAM device within seconds and with the accuracy of realistic MC simulations. Methods: The MC‐based algorithms we present incorporate photoelectric, Compton and Rayleigh effects for the interaction of low‐energy X‐rays. XIORT‐MC (X‐ray Intra‐Operative Radiation Therapy Monte Carlo) includes two dose calculation algorithms; a Woodcock‐based MC algorithm (WC‐MC) and a Hybrid MC algorithm (HMC), and it is implemented in CPU and in GPU. Detailed MC simulations have been generated to validate our tool in homogeneous and heterogeneous conditions with all INTRABEAM applicators, including three clinically realistic CT‐based simulations. A performance study has been done to determine the acceleration reached with the code, in both CPU and GPU implementations. Results: Dose distributions were obtained with the HMC and the WC‐MC and compared to standard reference MC simulations with more than 95% voxels fulfilling a 7%‐0.5 mm gamma evaluation in all the cases considered. The CPU‐HMC is 100 times more efficient than the reference MC, and the CPU‐WC‐MC is about 50 times more efficient. With the GPU implementation, the particle tracking of the WC‐MC is faster than the HMC, with the extraction of the particle's information from the PHSP file taking a major part of the time. However, thanks to the variance reduction techniques implemented in the HMC, up to 400 times less particles are needed in the HMC to reach the same level of noise than the WC‐MC. Therefore, in our implementation for INTRABEAM energies, the HMC is about 1.3 times more efficient than the WC‐MC in an NVIDIA GeForce GTX 1080 Ti card and about 5.5 times more efficient in an NVIDIA GeForce RTX 3090. Dose with noise below 5% has been obtained in realistic situations in less than 5 s with the WC‐MC and in less than 0.5 s with the HMC. Conclusions: The XIORT‐MC is a dose computation tool designed to take full advantage of modern GPUs, making possible to obtain MC‐grade accurate dose distributions within seconds. Its high speed allows a real‐time dose calculation that includes the realistic effects of the beam in voxelized geometries of patients. It can be used as a dose‐planning tool in the operating room during a XIORT treatment with any INTRABEAM device. [ABSTRACT FROM AUTHOR]

Case reports detailing the effects of targeted intraoperative radiation therapy (IORT) on patients with cardiac pacemakers (PMs) are rare. This growing population sub-group requiring IORT and lack of standardized guidelines necessitate more practical published research. An 81-year-old patient with clinical stage II, T1 N0 grade III, triple-negative invasive ductal carcinoma and an implanted single-lead chamber PM (VVIR mode, model: Biotronik, type Effecta SR) received targeted intraoperative radiotherapy at the time of wide local excision and sentinel lymph node biopsy. It presents the shortest distance between the outer diameter of the PM and IORT applicator in literature. Target IORT was performed utilizing an Intrabeam device (50 kV, Carl Zeiss Surgical, Oberkochen, Germany). This case elucidates the successful use of targeted IORT for breast-conserving surgery in a patient with a single ipsilateral chamber VVIR mode PM. No device failure or malfunction was reported for the PM before, during, or after the procedure. These findings support the use of targeted IORT for patients diagnosed with early-stage breast carcinomas who have a PM implanted. However, further research is needed to understand the safety of other methods and devices for IORT patients with cardiac implantable electronic devices.

Purpose: To evaluate local failure (LF) and toxicity after intraoperative radiation therapy (IORT) in pediatric solid tumors (ST)., Methods: A single-institution retrospective study of 96 pediatric patients (108 applications) with ST treated from 1995 to 2022 with IORT. LF was calculated via cumulative incidence function and overall survival (OS) by Kaplan-Meier method, both from the day of surgery., Results: Median age at time of IORT was 8 years (range: 0.8-20.9 years). Median follow-up for all patients and surviving patients was 16 months and 3 years, respectively. The most common histologies included rhabdomyosarcoma (n = 42), Ewing sarcoma (n = 10), and Wilms tumor (n = 9). Most (95%) received chemotherapy, 37% had prior external beam radiation therapy to the site of IORT, and 46% had a prior surgery for tumor resection. About half (54%) were treated with upfront IORT to the primary tumor due to difficult circumstances such as very young age or challenging anatomy. The median IORT dose was 12 Gy (range: 4-18 Gy), and median area treated was 24 cm 2 (range: 2-198 cm 2 ). The cumulative incidence of LF was 17% at 2 years and 23% at 5 years. Toxicity from IORT was reasonable, with postoperative complications likely related to IORT seen in 15 (16%) patients., Conclusion: Our study represents the largest and most recent analysis of efficacy and safety of IORT in pediatric patients with ST. Less than one quarter of all patients failed locally with acceptable toxicities. Overall, IORT is an effective and safe technique to achieve local control in patients with challenging circumstances., (© 2024 Wiley Periodicals LLC.)

Background: Pancreatic cancer has highly aggressive features, such as local recurrence that leads to significantly high morbidity and mortality and recurrence after successful tumour resection. Intraoperative radiation therapy (IORT), which delivers targeted radiation to a tumour bed, is known to reduce local recurrence by directly killing tumour cells and modifying the tumour microenvironment.Methods: Among 30 patients diagnosed with pancreatic cancer, 17 patients received IORT immediately after surgical resection. We investigated changes in the immune response induced by IORT by analysing the peritoneal fluid (PF) and blood of patients with and without IORT treatment after pancreatic cancer surgery. Further, we treated three pancreatic cell lines with PF to observe proliferation and activity changes.Results: Levels of cytokines involved in the PI3K/SMAD pathway were increased in the PF of IORT-treated patients. Moreover, IORT-treated PF inhibited the growth, migration, and invasiveness of pancreatic cancer cells. Changes in lymphocyte populations in the blood of IORT-treated patients indicated an increased immune response.Conclusions: Based on the characterisation and quantification of immune cells in the blood and cytokine levels in the PF, we conclude that IORT induced an anti-tumour effect by activating the immune response, which may prevent pancreatic cancer recurrence.Clinical Trial Registration: NCT03273374 . [ABSTRACT FROM AUTHOR]

Background: Intraoperative balloon electronic brachytherapy (IBEB) may provide potential benefit for local control of recurrent cerebral glioblastomas (GBMs). Methods: This is a preliminary report of an open-label, prospective, comparative cohort study conducted in two neurosurgical centers with ongoing follow-up. At recurrence, patients at one center (n = 15) underwent reresection with IBEB while, at the second center (n = 15), control subjects underwent re-resection with various accepted second-line adjuvant chemoradiotherapy options. A comparative analysis of overall survival (OS) and local progression-free survival (LPFS) following re-resection was performed. Exploratory subgroup analysis based on postoperative residual contrast-enhanced volume status was also done. Results: In the IBEB group, median LPFS after re-resection was significantly longer than in the control group (8.0 vs. 6.0 months; log rank 2 = 4.93, P = 0.026, P < 0.05). In addition, the median OS after second resection in the IBEB group was also significantly longer than in the control group (11.0 vs. 8.0 months; log rank 2 = 4.23, P = 0.04, P < 0.05). Conclusion: These hypothesis-generating results from a small cohort of subjects suggest putative clinical benefit in OS and LPFS associated with maximal safe re-resection of recurrent GBM with IBEB versus re-resection and standard adjuvant therapy, a hypothesis that deserves further testing in an appropriately powered clinical trial. [ABSTRACT FROM AUTHOR]

Purpose of Review: Adjuvant radiation represents a standard approach following breast conserving surgery. While traditionally delivered as whole breast irradiation (WBI), an alternative has emerged with the development of partial breast irradiation techniques. One such technique is intraoperative radiation therapy (IORT). The purpose of this review is to discuss the studies evaluating IORT as well as evaluating current guidelines and future directions. Recent Findings: Review of two randomized trials (TARGIT-A and ELIOT) demonstrates that breast cancer patients treated with IORT had a higher risk of local recurrence (LR). However, patients with low-risk features and IORT performed at the time of surgery had similar rates of LR at 5 years, with longer follow-up needed. IORT as a boost is promising, and studies are ongoing. Summary: Further studies are needed to validate the role of IORT and which patients are appropriate for IORT, and longer follow-up is needed. [ABSTRACT FROM AUTHOR]

Pheochromocytomas are rare catecholamine-secreting tumors with a high potential for recurrence post-surgery, necessitating prolonged follow-up. This case highlights the diagnostic and therapeutic challenges in managing recurrent pheochromocytoma. A 25-year-old female, with a history of left pheochromocytoma treated with adrenalectomy a decade earlier, presented with a right adrenal mass. Despite controlled hypertension, elevated urine metanephrines suggested recurrence. Imaging showed a right adrenal mass and suspicious left paraaortic lymph nodes, confirming the diagnosis of recurrent malignant pheochromocytoma in the left adrenal bed and right adrenal gland, with metastasis to the paraaortic lymph nodes. The patient underwent right adrenalectomy coupled with cytoreductive surgery (CRS) in the form of excision of left-sided adrenal bed recurrence and left paraaortic lymph node dissection, intraoperative radiation therapy (IORT), and hyperthermic intraperitoneal chemotherapy (HIPEC). On follow-up six years later, the patient remains free from recurrence. This case illustrates the importance of continued surveillance in pheochromocytoma patients, even those with a low-risk profile. The recurrence in this case, despite a smaller initial tumor size and no genetic predispositions, underscores the unpredictable nature of pheochromocytomas. The successful management with CRS, IORT, and HIPEC emphasizes the need for a personalized and multifaceted treatment approach. Pheochromocytoma patients, including those initially considered low risk, require long-term monitoring due to the risk of recurrence. The utilization of CRS, IORT, and HIPEC in this case was pivotal in managing the recurrent and metastatic malignant disease effectively, demonstrating the significance of a comprehensive, multidisciplinary treatment strategy in such complex cases. • Low risk pheochromocytoma patients require at least a 10-year follow-up. • Malignant pheochromocytoma is defined by the presence of extra-adrenal metastasis. • Recurrence of pheochromocytoma can be masked by controlled hypertension. • CRS, HIPEC, and IORT, a novel approach, was successful in treating pheochromocytoma. • HIPEC and IORT help achieve better local control and limit peritoneal spread. [ABSTRACT FROM AUTHOR]

Brain glioblastomas (GBM) are notorious for their early local recurrence despite of standard combined treatment. Technologies for recurrent GBM management require further development and research. Resection of malignant gliomas must be followed by an adjuvant treatment. Intraoperative balloon electronic brachytherapy (IBEB) has been recently introduced into clinical practice and could be successfully applied to recurrent GBM management. This article presents the initial results of recurrent GBM management with maximal safe resection followed by IBEB. Material and methods. Patients (n = 11) with recurrent GBM after standard combined treatment were managed with maximal safe microsurgical resection followed by IBEB. The follow-up period after IBEB ranged from 1 to 30 months. Results. The median overall survival for the entire study group of patients included in the statistical analysis (n = 9) was 27 months (range 17–47 months). In the subgroup of patients (n = 4) with contrast-enhanced tumor MRI volume after resection ≤ 2.5 cm3, the median local progression free survival (locPFS) was 21.25 months (range 10–30 months). Conclusion. Initial results in recurrent brain GBMs management with resection followed by IBEB seems to be promising, especially in case of contrast-enhanced tumor volume detected on MRI after resection is less than 2.5 cm3 without signs of multifocal tumor growth.

We evaluated the use of ultrasound imaging within a brachytherapy applicator as a method for applicator positioning, evaluation, and treatment planning in a series of in vitro , cadaver, and human studies. We evaluated the performance of a prototype system comprising a small ultrasound imaging catheter inserted within the lumen of a balloon brachytherapy catheter. We tested the device in an ultrasound phantom, in human breast tissue, and in an endoscopic ultrasound catheter in cadaveric breast tissue. We evaluated the visualization of adjacent tissue to consider future development of a similar system for use in brachytherapy and intraoperative radiation therapy. Based on the ultrasound images obtained in an ultrasound phantom, cadaveric breast, and human participants, we observed that an ultrasound imaging catheter placed within the lumen of a brachytherapy applicator can effectively image adjacent tissue, ribs, and air voids, with appropriate quality to support clinical use. We observed high correlation in clinically useful information detected on ultrasound and comparative CT, with ultrasound spatial resolution near 1 mm (spatially variant). The findings from our pilot work suggest that real-time ultrasound imaging, operated from within the applicator, is a promising technique for image guidance and treatment planning during brachytherapy and intraoperative radiation therapy. Further expansion of this technology for clinical use will require development of a cohesive system of components to suit specific clinical applications. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical efficacy of surgical excision combined with low-energy X-ray irradiation in the treatment of ear keloids. Methods: Clinical data of 32 cases of ear keloid lesions that received surgical treatment alone or surgery combined with radiotherapy from March 2019 to November 2022 in the Department of Otorhinolaryngology Head and Neck Surgery of the Tianjin First Central Hospital were retrospectively analyzed. Among them, 10 cases received radiotherapy and 22 cases did not receive radiotherapy. The radiotherapy group received irradiation with a large divided dose of 50 kV low-energy X-rays. The mode of fractionation radiotherapy was as follows: the first was 10 Gy of intraoperative radiation therapy and the second was 8 Gy on the 3rd postoperative day for a total of 18 Gy. The local efficacy and skin radiation reaction were observed at a follow-up of 8-52 months. Results: The median follow-up was 26 months, and as of the date of the last follow-up, 9 cases were cured and 1 case was ineffective in the radiotherapy group, with an effective rate of 90.0%, while 9 cases were cured and 13 cases were ineffective in the no-radiotherapy group, with an effective rate of 40.9%. The recurrence of ear keloids was not related to the side, site, or etiology of the patient's onset（ P >0.05）. Recurrence was related to whether or not the patients received radiotherapy（ χ ²=4.885, P <0.05）, and the recurrence rate in the radiotherapy group（10.0%） was significantly lower than that in the non-radiotherapy group（59.1%）. Conclusion: Surgical excision combined with low-energy X-ray irradiation therapy is an effective method of treating keloids in the ear, especially with intraoperative radiation therapy can achieve more satisfactory results., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: The standard treatment for recurrent or persistent anal squamous cell carcinoma is surgical salvage, but disease control and survival are suboptimal., Patients/methods: Patients treated for recurrent or persistent anal squamous cell carcinoma at our institution from 2002 to 2022 were included. Patients were classified by type of salvage treatment received: surgery alone vs. reirradiation followed by surgery and by whether they received intraoperative radiation at the time of surgery. Clinical and pathologic variables were collected and assessed for association with risk of second local recurrence and death from any cause., Results: Sixty four patients were included; 55(85.9%) were treated with surgery alone and 9 (14.1%) were treated with reirradiation followed by surgery. Median (IQR) follow up from the time of salvage treatment was 40.0 (20.3-68.0) months. The 3-year cumulative incidence of second local recurrence (95% CI) after salvage surgery was 36% (24%-48%); 39% (26%-52%) for patients treated with surgery alone and 15% (0.46%-51%) for patients treated with reirradiation followed by surgery. Factors associated with increased second local recurrence after salvage surgery included a locoregional recurrence, lymphovascular space invasion and positive surgical margins. The 3-year overall survival (95% CI) after salvage surgery was 70% (59%-83%); 68% (7%-56%) after surgery alone and 89% (10.5%-70.6%) after reirradiation followed by surgery. Factors associated with worse overall survival included male sex, a larger recurrent tumor and positive surgical margins., Conclusions: Approximately 60% of patients achieved pelvic control after salvage therapy for recurrent or persistent anal squamous cell carcinoma. Although receipt of reirradiation and intraoperative radiation were not associated with improved second local recurrence or overall survival in our cohort, patients with positive surgical margins and lymphovascular space invasion on surgical pathology had higher rates of pelvic recurrence after salvage surgery and may benefit from escalated salvage therapy., Competing Interests: Disclosure None., (Copyright © 2023 Elsevier Inc. All rights reserved.)